Antiparasitic Agents, Anthelmintics

Abstract

Human infections caused by worms (helminths) represent one of the most important public health problems in the world. Helminths form three main categories or phyla: Platyhelminths, flatworms; Aschelminthes, roundworms; and Nemathelminthes, thorny‐headed worms. Substantial progress in the discovery and development of anthelmintic drugs has been made. Effective agents are available for most human gastrointestinal infections; however, drugs that are effective in treating the extraintestinal complications of many helminthic infections are still needed. Agents include praziquantel for the treatment of flukes, eg, C. sinensis ; tapeworms, eg, H. nana ; and larval stage (cysticercosis); oxamniquine for the treatment of flukes ( S. mansoni ); metrifonate for the treatment of blood flukes ( Schistosoma haematobium ); bithionol for the treatment of lung flukes ( Paragonimu westermani ), sheep liver flukes ( Fasciola hepatica ); tetrachloroethylene for the treatment of intestinal fluke ( Fasicolopsis buski ); niclosamide for the treatment of tapeworms ( T. saginata, T. solium , and D. latum ); quinacrine for the treatment of pork tapeworm ( Taenia solium ); piperazine citrate for the treatment of roundworms ( Ascaris lumbricoides ); diethylcarbamazine citrate for the treatment of lymphatic filariases ( Wuchereria bancrofti, Loa loa , and other filaria); pyrantel pamoate for the treatment of pinworms ( Enterobius vermiculus ), roundworms ( Ascaris lumbricoides ), hookworms ( Ancyclostoma duodenale, Necator americanus ); mebendazole for the treatment of (whipworms ( Trichuris trichiura ), hookworms ( Ancylostoma duodenale, Nector americanus ), filariasis ( Mansonella perstans ), roundworm ( Ascaris lumbricoides ), Trichinosis ( Trichinella spiralis ); thiabendazole for the treatment of hookworms ( Trichostrongylus sp., cutaneous larva migrans, Angiostrongylus costaricensis , and Strongyloides stercoralis ); and ivermectin for the treatment of filariasis ( Onchocerca volvulus ). Frequently, the treatment of helminthic diseases requires adjunct medication eg, antihistamines and corticosteroids. Allergic reactions are commonly seen as a result of tissue invasion by worms or as a consequence of anthelmintic therapy. Three main species of blood flukes cause schistosomiasis in humans: Schistosoma haematobium, S. mansoni , and S. japonicum . The effectiveness of antischistosomal drugs depends on the reduction or arrest of egg production. Infection only occurs as a result of the penetration of the intact skin by free‐swimming cercaria. After they develop to preadult forms in the skin and lung, the parasites migrate through host blood vessels to various tissues. Adult worms that are approximately 2 cm in length remain paired within the portal or intestinal vasculature of the host. The female, however, travels as far as possible toward the capillary beds to lay eggs, a portion of which embolize to the liver and induce granuloma formation. During the early stages of the disease, patients may experience fever, gastrointestinal distress, headache, and fatigue. In later stages of the disease, signs of hepatic fibrosis and ascites are seen. The number of worm pairs found in a patient may vary from a few to over 100. In untreated patients, adult worms are now generally assumed to live less than 5–10 years. Praziquantel , C 19 H 24 N 2 O 2 , can be used to treat schistosomiasis caused by any one of the three major species. Praziquantel is an acylated pyrazino–isoquinoline derivative that has replaced the traditional (and more toxic) trivalent antimonial compounds.